Anticoagulation & bleeding

Starting anticoagulation

Systemic anticoagulation should be provided for all patients on ECMO in the absence of bleeding and no anticipated or recent surgery. Anticoagulation practices are based on patient bleeding risk profiles. Our standard agent is heparin.

Non-bleeding patients

• Platelets to be maintained > 50,000
• Systemic heparin APTT target is 50-70

Bleeding and post-operative patients

This includes: post-surgical; post-procedural and spontaneously bleeding patients

• Aggressively replace all clotting element deficiencies
• Give cryoprecipitate to target fibrinogen > 1.5
• Give platelets to target count >80,000 or normal MA (maximum amplitude) on TEG
• Give Prothrombinex and FFP to target INR <1.3 or normal R time on TEG

Heparin should not be recommended until all bleeding has stopped for at least 12 to 24 hours (assessed on an individual case basis). Even longer times without anticoagulation are acceptable depending on the balance of risk and benefits.

Scheduled essential surgery or procedure (not yet bleeding) not including scheduled VA decannulation

• Cease heparin for 4 hours prior
• Replace deficits as stated above
• Start tranexamic acid (anti-fibrinolytic) prior to surgery or procedure

Management of severe bleeding

Ongoing severe bleeding (despite above) should be managed in consultation with the ECMO consultant, haematologist, and the relevant surgical specialists.

Options to consider include

• Surgery or Interventional Radiology
• Protamine: may be used after discussion with the ECMO consultant if unreversed heparin is definitively implicated in bleeding (TCT and reptilase tests may support a clinical diagnosis). Protamine may promote circuit thrombosis in Bioline coated components (particularly HLS or PLS Oxygenators) and should be used with utmost caution. Where protamine is to be administered a pre-primed circuit and capability for emergent circuit change must be arranged. Protamine should not be used to treat bleeding not temporally related to heparin.
• Tranexamic acid (see below)
• Factor VIIa In consultation with the haematologist
• Palliation

The usual focus on haemorrhage control should be exercised like in any other massive transfusion scenario. In addition, the heater of the ECMO circuit may effectively be used to maintain normothermia. Access insufficiency whilst at times an early indicator of bleeding, its absence can not be used to rule out significant haemorrhage. The blood flow may need to be adjusted to avoid ongoing access insufficiency during blood volume resuscitation.

Heparin

Heparin is used as the standard anticoagulant agent in the vast majority of patients. Anticoagulation targets are adjusted from 50-70 (60-80) downwards according to risk. If bleeding is a real concern, a low dose of 500 U/hr without measurable anticoagulant effect or no anticoagulation at all may be tolerated for several days.

Heparin Induced Thrombocytopenia (HITS) on ECMO is rare. However, thrombocytopenia on ECMO is common and therefore confounding one of the 4 T criteria to assess the probability of HITS. Heparin should be ceased and platelet counts should not be treated if HITS is clinically suspected. Circuit components are Bioline coated which contains heparin. Patients who have confirmed HITS on ECMO have been successfully managed on existing circuits despite the presence of heparin bonding. In these cases, systemic anticoagulation is maintained with parenteral direct thrombin inhibitors (Lepirudin, Bivalirudin, and Argatroban) in close consultation with Haematology. If ongoing concerns prevail a non-heparin bonded circuit can be made available.

Bivalirudin

Reference to the Alfred protocol for the use of bivalirudin is made here. Generally, bivalirudin is used if HITS is suspected or in case of thrombotic complications in VV ECMO patients (under heparin anticoagulation). Currently, the cost of bivalirudin anticoagulation is substantially higher than with heparin.

Tranexamic Acid

Using tranexamic acid for refractory bleeding and or in the setting of surgery may be reasonable. it is important to assess hyperfibrinolytic states that preceded the bleeding and are caused by circuit driven hyperfibrinolysis and bleeding which is treated by changing the circuit and factor replacement primarily not TXA. It is not without risk to use TXA, in particular, circuit clotting is of con

• Prepare 50 ml syringe with “neat” TXA solution (5g). i.e. 10 ampoules of TXA 500 mg in 5 ml
• Loading dose of 12.5 mg/kg given over 30 minutes provided no other clotting factors being given concurrently
• Maintenance infusion of 6.5 mg/kg/hour started immediately after loading dose and continuing until syringe empty (approx. 10 hours) or bleeding has ceased for 2 hours
• Reduce maintenance infusion to 3 mg/kg/hour if administration is continuing beyond 5 grams.
• Maintenance infusion rate to be reduced if renal or hepatic dysfunction present. Loading dose should remain unchanged
• The main risk with this therapy is acute thrombotic events including circuit thrombosis

Threshold for blood transfusion

ALL patients should have a current crossmatch

Red Blood Cell Transfusion

Specific transfusion triggers for RBC are not used, however commonly, clinicians use a trigger of 80g/L. In the case of refractory hypoxaemia (SaO₂ < 88%) despite optimised VV ECMO support, higher transfusion thresholds (Hb > 10 g/dL) may be used to optimise DO₂. See hypoxia on VV ECMO.

Platelets

Thrombocytopenia in the setting of ECMO is common yet needs to be carefully determined. Bleeding and or intravascular consumption in particular need to be excluded and HITS to be considered. Generally, platelets are kept above 80/nl and at least 50/nl depending on the cause and the bleeding risk profile.